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Am J Respir Cell Mol Biol. 2010 Jun;42(6):667-75. doi: 10.1165/rcmb.2008-0429OC. Epub 2009 Jul 27.

Interleukin-13 regulates secretion of the tumor growth factor-{beta} superfamily cytokine activin A in allergic airway inflammation.

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1
Department of Immunology, Monash University, Commercial Road, Melbourne, VIC 3004 Australia. charles.hardy@med.monash.edu.au

Abstract

Activin A is a member of the TGF-beta superfamily and plays a role in allergic inflammation and asthma pathogenesis. Recent evidence suggests that activin A regulates proinflammatory cytokine production and is regulated by inflammatory mediators. In a murine model of acute allergic airway inflammation, we observed previously that increased activin A concentrations in bronchoalveolar lavage (BAL) fluid coincide with Th2 cytokine production in lung-draining lymph nodes and pronounced mucus metaplasia in bronchial epithelium. We therefore hypothesized that IL-13, the key cytokine for mucus production, regulates activin A secretion into BAL fluid in experimental asthma. IL-13 increased BAL fluid activin A concentrations in naive mice and dose dependently induced activin A secretion from cultured human airway epithelium. A key role for IL-13 in the secretion of activin A into the BAL fluid during allergic airway inflammation was confirmed in IL-13-deficient mice. Eosinophils were not involved in this response because there was no difference in BAL fluid activin A concentrations between wild-type and eosinophil-deficient mice. Our data highlight an important role for IL-13 in the regulation of activin A intraepithelially and in BAL fluid in naive mice and during allergic airway inflammation. Given the immunomodulatory and fibrogenic effects of activin A, our findings suggest an important role for IL-13 regulation of activin A in asthma pathogenesis.

PMID:
19635933
DOI:
10.1165/rcmb.2008-0429OC
[Indexed for MEDLINE]
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